Dimethyl malonate → Methyl 8-hydroxy-6-oxo-5,6-dihydropyrido[2,3-b]pyrazine-7-carboxylate

HRID 2197507Notes

Reaction equation

HRID 2197507 reaction equation
C[O-].[Na+].[C:4]([O:11]C)(=O)[CH2:5][C:6]([O:8][CH3:9])=[O:7].[NH2:13][C:14]1[C:15]([C:20](OC)=[O:21])=[N:16][CH:17]=[CH:18][N:19]=1>CO>[CH3:9][O:8][C:6]([C:5]1[C:4](=[O:11])[NH:13][C:14]2=[N:19][CH:18]=[CH:17][N:16]=[C:15]2[C:20]=1[OH:21])=[O:7]

Participants

5

Reactant 3

HCID 7943Dimethyl malonateHCID 72669Methyl 3-aminopyrazinecarboxylateHCID 10942334Sodium Methoxide

Product 1

HCID 57998840Methyl 8-hydroxy-6-oxo-5,6-dihydropyrido[2,3-b]pyrazine-7-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium methoxide (6.5 ml) (30% by weight in methanol) was dissolved in methanol (75 ml) at room temperature. Dimethyl malonate (3.7 ml) was added dropwise at ambient temperature over a period of 20 minutes and the reaction stirred at ambient temperature for 1 hour. Methyl 3-aminopyrazine-2-carboxylate (5.0 g) was added in portions at ambient temperature over a period of 40 minutes. The reaction mixture was heated to reflux for 3 days, and then allowed to cool. The solvent was concentrated. The residue was dissolved in water and acidified with concentrated hydrochloric acid (36% by weight in water). The precipitate was isolated, washed with water, methanol and ethyl acetate, and dried under high vacuum to give 8-hydroxy-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazine-7-carboxylic acid methyl ester as a beige solid (4.16 g). 1H-NMR (d6-DMSO): 3.80 (s, 3H), 8.59 (s, 1H), 8.70 (s, 1H) ppm.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 3 days
  3. temperatureto cool
  4. concentrationThe solvent was concentrated
  5. dissolutionThe residue was dissolved in water
  6. customThe precipitate was isolated
  7. washwashed with water, methanol and ethyl acetate
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-48647d67f082459f844aa2b0796e5c60
Source dataset
uspto-grants-2012_12
Patent number
US08338598B2

Reaction notes

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